Pascual M, Nieto A, López-Nevot M A, Ramal L, Matarán L, Caballero A, Alonso A, Martín J, Zanelli E
Instituto de Parasitología y López-Neyra, Biomedicina, CSIC, Granada, Spain.
Arthritis Rheum. 2001 Feb;44(2):307-14. doi: 10.1002/1529-0131(200102)44:2<307::AID-ANR47>3.0.CO;2-K.
To evaluate the contributions of HLA-DQ and -DR polymorphisms to susceptibility to rheumatoid arthritis (RA) in a population in southern Spain, and to compare the value of the shared epitope (SE) and RA protection (RAP) models in accounting for the HLA class II region's contribution to RA predisposition.
One hundred sixty RA patients and 153 healthy controls were typed for HLA-DRB1 and -DQB1 using high-resolution DNA techniques. Distributions of predisposing DRB1 alleles in patients and control subjects according to the SE model were compared with distributions of predisposing DQ and protective DERAA-positive DRBI alleles according to the RAP model.
DQ3 (DQBI03 and 04 combined with DQA103) and DQ5 (DQB10501/DQA10101) alleles predisposed individuals to RA independently of SE-positive DRB1 alleles. DQ3/3-homozygous individuals had the strongest risk of developing RA. DQ3 molecules predisposed to RA more than did DQ5 molecules. The weaker predisposition mediated by DQ5 included the DRB11001-carrying haplotype; no DRB11001-homozygous patients were observed. DRBI0401 played a unique role in the contribution of DQ3-DR4 haplotypes to RA, in spite of its low frequency in southern Spain.
The low prevalences of RA and of mild disease observed in Spain, and in southern Europe in general, can be explained in great part by the low frequency of DQ3-DR4 haplotypes, especially those carrying DRB1*0401. However, the overall distribution of HLA-DQ and -DR alleles in RA patients compared with control subjects is similar to that in other European and North American populations. A model involving both DQ and DR can best account for the contribution of HLA to RA.
评估HLA-DQ和-DR基因多态性对西班牙南部人群类风湿关节炎（RA）易感性的影响，并比较共享表位（SE）模型和RA保护（RAP）模型在解释HLA II类区域对RA易感性贡献方面的价值。
采用高分辨率DNA技术对160例RA患者和153例健康对照进行HLA-DRB1和-DQB1分型。根据SE模型比较患者和对照中易感DRB1等位基因的分布，以及根据RAP模型比较易感DQ和保护性DERAA阳性DRBI等位基因的分布。
DQ3（DQBI03和04与DQA103组合）和DQ5（DQB10501/DQA10101）等位基因使个体易患RA，独立于SE阳性DRB1等位基因。DQ3/3纯合个体患RA的风险最强。DQ3分子比DQ5分子更易使个体患RA。由DQ5介导的较弱易感性包括携带DRB11001的单倍型；未观察到DRB11001纯合患者。尽管DRBI0401在西班牙南部频率较低，但在DQ3-DR4单倍型对RA的贡献中发挥了独特作用。
在西班牙以及整个南欧观察到的RA低患病率和轻度疾病患病率，在很大程度上可以用DQ3-DR4单倍型的低频率来解释，尤其是那些携带DRB1*0401的单倍型。然而，与对照相比，RA患者中HLA-DQ和-DR等位基因的总体分布与其他欧洲和北美人群相似。一个涉及DQ和DR的模型最能解释HLA对RA的贡献。
